1. Field of the Invention
The present invention relates to methods and compositions for testing pancreatic exocrine function. More specifically, it relates to the use of the vitamin B.sub.12 ingestion system as a means of measuring pancreatic exocrine function.
2. Prior Art
The human pancreas contains endocrine portions and an exocrine portion. The endocrine portions actually consist of a multitude of small islets that synthesize and release hormones into the blood. The exocrine portion carries the endocrine islets and makes up the bulk of the pancreas. When functioning properly, the exocrine portion synthesizes a number of digestive enzymes such as amylase, trypsin, chymotrypsin, elastase, lipase, and others. These enzymes are released into the upper part of the small intestine and are essential for proper digestion and nourishment.
On occasion the exocrine portion of the pancreas may be caused to malfunction. Such malfunction may be due to damage caused in a variety of ways, including chronic alcoholism, trauma, and pancreatic cancer. Due to the fact that the pancreas is located deep in the abdomen it is extremely difficult to evaluate clinically. X-rays and scans of the pancreas are discernably abnormal in only a relatively small proportion of patients with actual pancreatic exocrine insufficiency.
Several tests of pancreatic exocrine function are currently available. However, such tests are time consuming, cumbersome and inconvenient. One prior art test involves measuring the amount of fat in feces. This fecal fat test is based on the fact that fecal fat is increased in the absence of the pancreatic exocrine enzyme lipase which is required for the digestion and absorption of fat in the intestine. To accomplish this test the patient must save all of his feces for 72 hours and the feces must then be analyzed for fat in the laboratory. This test is unpleasant for the patient and for laboratory personnel and, even then, it is not available at many hospitals. Furthermore, this fecal fat test lacks specificity to pancreatic exocrine insufficiency, since it also provides abnormal results in a variety of intestinal diseases such as Crohn's disease and sprue.
Another prior art test, duodenal intubation, involves placing a tube into the upper small intestine via the mouth and stomach and then collecting pancreatic juice which is subsequently analyzed for volume, bicarbonate and pancreatic enzymes. This test is time consuming, expensive, inconvenient and unpleasant for the patient, and again, it is available at only a relatively small number of medical centers. It is therefore seen that there is presently no convenient easily applied test for pancreatic exocrine function.
It has been noted, for example, employing standard Schilling tests that B.sub.12 is malabsorbed by about 50% of patients diagnosed to have pancreatic exocrine insufficiency. However, B.sub.12 malabsorbtion by itself is not a reliable indication of pancreatic exocrine dysfunction as B.sub.12 absorption is not abnormal in more than about one-half of patients with such disfunction, and further, as B.sub.12 absorption is also abnormal in cases of pernicious anemia and also as a result of a number of intestinal diseases.
The Schilling test, noted above, utilizes labelled B.sub.12, for example, B.sub.12 including a radioactive cobalt isotope, to measure and evaluate absorption of B.sub.12 by the digestive system. A modified or dual labelling Schilling test is commercially available, which uses two differently labelled forms of B.sub.12, one of which is bound to intrinsic factor, and the other of which is unbound. However, such tests utilizing labelled B.sub.12 have at no time been used to independently evaluate pancreatic exocrine function.
For many years it was believed that ingested vitamin B.sub.12 was bound in the form of a complex to a protein known as intrinsic factor (IF) present in the gastric juices of the stomach. It was further believed that this IF-B.sub.12 complex remained intact until it attached to specific receptors located at the end of the small intestine at which receptors the B.sub.12 was unbound and absorbed into the body. It has now been determined that this model for B.sub.12 ingestion is incorrect and that use of the correct B.sub.12 ingestion model can now serve as the basis of accurately evaluating pancreatic exocrine function.